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Prospective validation of VEGF and eNOS polymorphisms as predictors of first-line bevacizumab efficacy in patients with metastatic colorectal cancer
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Prospective validation of VEGF and eNOS polymorphisms as predictors of first-line bevacizumab efficacy in patients with metastatic colorectal cancer
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Prospective validation of VEGF and eNOS polymorphisms as predictors of first-line bevacizumab efficacy in patients with metastatic colorectal cancer
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Journal Article
Prospective validation of VEGF and eNOS polymorphisms as predictors of first-line bevacizumab efficacy in patients with metastatic colorectal cancer
2023
Overview
Bevacizumab (Bev) plus chemotherapy is a standard first-line treatment in metastatic colorectal cancer (mCRC), however to date no predictive factors of response have been identified. Results of our previous analysis on patients enrolled in a randomized prospective phase III multicenter study (ITACa study) showed a predictive value of Vascular Endothelial Growth Factor (
VEGF
) polymorphism (
VEGF
+ 936), a 27-nucleotide variable number tandem repeat (VNTR) of the endothelial nitric oxide synthase (
eNOS
) gene and
eNOS
+ 894 polymorphism. mCRC patients, treated with Bev plus chemotherapy, were included in this prospective validation trial.
eNOS
+ 894G > T was analyzed by Real time PCR, while the
eNOS
VNTR and
VEGF
+ 936C > T were determined by standard PCR and direct sequencing analysis. These polymorphisms were assessed in relation to progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). These three polymorphisms were not predictive of PFS (
p
0.91, 0.59 and 0.09, respectively), and OS (
p
0.95, 0.32 and 0.46, respectively). Moreover, the haplotype analyses did not confirm what was found in our previous study; patients bearing a specific haplotype of
eNOS
had not significantly improved outcomes. This prospective study failed to validate the predictive impact of
eNOS
and
VEGF
polymorphisms for response to Bev plus first-line chemotherapy in mCRC patients.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 692/4028
/ Antineoplastic Combined Chemotherapy Protocols - adverse effects
/ Colonic Neoplasms - drug therapy
/ Colorectal Neoplasms - drug therapy
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - pathology
/ Fluorouracil - therapeutic use
/ Humanities and Social Sciences
/ Humans
/ Nitric Oxide Synthase Type III - genetics
/ Polymorphism, Single Nucleotide
/ Rectal Neoplasms - drug therapy
/ Science
/ Survival
